Determination of the mechanisms of immune alteration and increased susceptibility for respiratory infections among opiate drug abusers will better aid in understanding the link between the risk of intravenous drug abuse (IVDU) and the course of disease for the deadly AIDS epidemic. Severe abnormalities in cell mediated immunity exist in both IV drug abusers as well as AIDS patients. Pulmonary infections are the most common infections among IV drug abusers and among the most common and deadly for AIDS patients. The objective of the research proposal is to investigate the mechanisms of immune alteration and pathogenesis which leads to the observation of increased pneumonia in chronic morphine treated animals. We will test the hypothesis that under conditions of chronic morphine 1) Opiate drugs suppress local immune functions by rendering macrophages, lymphocytes, or neutrophils unresponsive or ineffective to antigenic stimulation and 2) Mechanisms of action involve modulation of cytokine expression. This will be accomplished by utilizing a swine model for chronic morphine administration to investigate the specific aims of: 1) Comparing in vivo the dynamic changes in cell populations and phenotypes that occur during SHV- 1 and Pasteurella multocida infection in swine administered chronic morphine and controls. 2) Testing pulmonary immune cell function and trafficking in vivo and in vitro from chronic morphine treated swine and determining the naloxone reversible nature of observable function changes. 3) Determine the naloxone reversibility of increased morphine associated pneumonia. 4) Test the cytokine expression at the local inflammatory sites of morphine associated pneumonia. 5) Determine if the treatment drug methadone also alters the course of viral/bacterial pneumonia.